JPS6363546B2 - - Google Patents
Info
- Publication number
- JPS6363546B2 JPS6363546B2 JP7036579A JP7036579A JPS6363546B2 JP S6363546 B2 JPS6363546 B2 JP S6363546B2 JP 7036579 A JP7036579 A JP 7036579A JP 7036579 A JP7036579 A JP 7036579A JP S6363546 B2 JPS6363546 B2 JP S6363546B2
- Authority
- JP
- Japan
- Prior art keywords
- glyoxylic acid
- formula
- multiplet
- pyrrolidine
- optically active
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- HHLFWLYXYJOTON-UHFFFAOYSA-N glyoxylic acid Chemical class OC(=O)C=O HHLFWLYXYJOTON-UHFFFAOYSA-N 0.000 claims description 20
- -1 Glyoxylic acid ester Chemical class 0.000 claims description 16
- 125000003118 aryl group Chemical group 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 10
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- RNVVYVPDHMKDTL-UHFFFAOYSA-N methyl 2-(hydroxymethoxy)acetate Chemical compound COC(=O)COCO RNVVYVPDHMKDTL-UHFFFAOYSA-N 0.000 description 5
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- BEYTUOFWMWNNTA-UHFFFAOYSA-N 1-(2-phenyl-1,3,5,6,7,7a-hexahydropyrrolo[1,2-c]imidazol-3-yl)ethanone Chemical compound CC(=O)C1N2CCCC2CN1C1=CC=CC=C1 BEYTUOFWMWNNTA-UHFFFAOYSA-N 0.000 description 2
- XNIHZNNZJHYHLC-UHFFFAOYSA-M 2-oxohexanoate Chemical compound CCCCC(=O)C([O-])=O XNIHZNNZJHYHLC-UHFFFAOYSA-M 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 238000000921 elemental analysis Methods 0.000 description 2
- MCHWKJRTMPIHRA-UHFFFAOYSA-N n-(pyrrolidin-2-ylmethyl)aniline Chemical compound C1CCNC1CNC1=CC=CC=C1 MCHWKJRTMPIHRA-UHFFFAOYSA-N 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- DJSCQCGHDWBAMG-VIFPVBQESA-N (2r)-2-hydroxy-2-phenylpropanal Chemical compound O=C[C@@](O)(C)C1=CC=CC=C1 DJSCQCGHDWBAMG-VIFPVBQESA-N 0.000 description 1
- UWCWUCKPEYNDNV-UHFFFAOYSA-N 2,6-dimethyl-n-(pyrrolidin-2-ylmethyl)aniline Chemical compound CC1=CC=CC(C)=C1NCC1NCCC1 UWCWUCKPEYNDNV-UHFFFAOYSA-N 0.000 description 1
- ZUCOIFUQBLMWEN-UHFFFAOYSA-N 2-(hydroxymethoxy)acetic acid Chemical compound OCOCC(O)=O ZUCOIFUQBLMWEN-UHFFFAOYSA-N 0.000 description 1
- TYEYBOSBBBHJIV-UHFFFAOYSA-M 2-oxobutanoate Chemical compound CCC(=O)C([O-])=O TYEYBOSBBBHJIV-UHFFFAOYSA-M 0.000 description 1
- QHKABHOOEWYVLI-UHFFFAOYSA-N 3-methyl-2-oxobutanoic acid Chemical compound CC(C)C(=O)C(O)=O QHKABHOOEWYVLI-UHFFFAOYSA-N 0.000 description 1
- NCFACXDXEKYAOF-UHFFFAOYSA-N 4-methyl-n-(pyrrolidin-2-ylmethyl)aniline Chemical compound C1=CC(C)=CC=C1NCC1NCCC1 NCFACXDXEKYAOF-UHFFFAOYSA-N 0.000 description 1
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 230000002862 amidating effect Effects 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- FWTXWYXPXGKVJG-UHFFFAOYSA-N atrolactamide Chemical compound NC(=O)C(O)(C)C1=CC=CC=C1 FWTXWYXPXGKVJG-UHFFFAOYSA-N 0.000 description 1
- 229950011225 atrolactamide Drugs 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 239000012024 dehydrating agents Substances 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- IVRYBIASBRGJQI-UHFFFAOYSA-N methyl 2-phenyl-1,3,5,6,7,7a-hexahydropyrrolo[1,2-c]imidazole-3-carboxylate Chemical compound COC(=O)C1N2CCCC2CN1C1=CC=CC=C1 IVRYBIASBRGJQI-UHFFFAOYSA-N 0.000 description 1
- 239000010446 mirabilite Substances 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- BRWGMAJNFKHZDG-UHFFFAOYSA-N n-(pyrrolidin-1-ylmethyl)aniline Chemical compound C1CCCN1CNC1=CC=CC=C1 BRWGMAJNFKHZDG-UHFFFAOYSA-N 0.000 description 1
- SRYXYJQVUDCZIG-UHFFFAOYSA-N n-(pyrrolidin-2-ylmethyl)naphthalen-1-amine Chemical compound C=1C=CC2=CC=CC=C2C=1NCC1CCCN1 SRYXYJQVUDCZIG-UHFFFAOYSA-N 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- ANRQGKOBLBYXFM-UHFFFAOYSA-M phenylmagnesium bromide Chemical compound Br[Mg]C1=CC=CC=C1 ANRQGKOBLBYXFM-UHFFFAOYSA-M 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- BWQSEDZTBKYDHS-UHFFFAOYSA-N propyl 2-oxoacetate Chemical compound CCCOC(=O)C=O BWQSEDZTBKYDHS-UHFFFAOYSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- RSIJVJUOQBWMIM-UHFFFAOYSA-L sodium sulfate decahydrate Chemical compound O.O.O.O.O.O.O.O.O.O.[Na+].[Na+].[O-]S([O-])(=O)=O RSIJVJUOQBWMIM-UHFFFAOYSA-L 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
【発明の詳細な説明】
本発明はグリオキシル酸誘導体及びその製造法
に関するものである。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to glyoxylic acid derivatives and methods for producing the same.
さらに詳しくは本発明は一般式(1)
（式中、Ａはアリール基、Ｒはアルキル基を表わ
す）
で示される光学活性もしくはラセミのグリオキシ
ル酸誘導体に関するものとグリオキシル酸エステ
ルもしくはグリオキシル酸エステルヘミアセター
ルと一般式(2)
（式中、Ａはアリール基を表わす）
で示される光学活性もしくはラセミの２−（Ｎ置
換アミノメチル）ピロリジンを反応させることに
より一般式(1)で示される光学活性もしくはラセミ
のグリオキシル酸誘導体（以後グリオキシル酸誘
導体と略称する）を製造する方法に関するもので
ある。 More specifically, the present invention is based on the general formula (1) (In the formula, A represents an aryl group and R represents an alkyl group) Those related to optically active or racemic glyoxylic acid derivatives represented by the formula: glyoxylic acid ester or glyoxylic acid ester hemiacetal and the general formula (2) (In the formula, A represents an aryl group) By reacting an optically active or racemic 2-(N-substituted aminomethyl)pyrrolidine represented by the formula (1), an optically active or racemic glyoxylic acid derivative represented by the general formula (1) ( This invention relates to a method for producing glyoxylic acid derivatives (hereinafter abbreviated as glyoxylic acid derivatives).
本発明の対象であるグリオキシル酸誘導体は新
規化合物であり、農薬、医薬の中間原料となり得
るものである。 The glyoxylic acid derivative that is the object of the present invention is a new compound and can be used as an intermediate raw material for agricultural chemicals and medicines.
例えば参考例に掲げたごとく光学活性なグリオ
キシル酸誘導体から高い光学純度を有するα−ヒ
ドロキシアルデヒドを製造することができる。こ
の化合物は酸化してカルボン酸とした後、アミド
化することにより、医薬品として用いられる鎮痛
剤「アトロラクタミド」に誘導し得る。 For example, as shown in Reference Examples, α-hydroxyaldehyde having high optical purity can be produced from optically active glyoxylic acid derivatives. By oxidizing this compound to a carboxylic acid and then amidating it, it can be derived into the analgesic drug "atrolactamide" used as a pharmaceutical.
本発明は新規にしてかつ有用なグリオキシル酸
誘導体及びその製造法を提供するものである。 The present invention provides a novel and useful glyoxylic acid derivative and a method for producing the same.
本発明において用いられるグリオキシル酸エス
テルもしくはグリオキシル酸エステルヘミアセタ
ールとしては通常アルキルエステルが用いられ、
例えばグリオキシル酸メチル、グリオキシル酸エ
チル、グリオキシル酸ｎ−プロピル、グリオキシ
ル酸イソプロピル、グリオキシル酸ｎ−ブチル、
ヒドロキシメトキシ酢酸メチル、ヒドロキシエト
キシ酢酸エチル、ヒドロキシｎ−プロポキシ酢酸
ｎ−プロピル、ヒドロキシイソプロポキシ酢酸イ
ソプロピル、ヒドロキシｎ−ブトキシ酢酸ｎ−ブ
チル等を挙げることができる。 As the glyoxylate ester or glyoxylate hemiacetal used in the present invention, an alkyl ester is usually used,
For example, methyl glyoxylate, ethyl glyoxylate, n-propyl glyoxylate, isopropyl glyoxylate, n-butyl glyoxylate,
Methyl hydroxymethoxy acetate, ethyl hydroxyethoxy acetate, n-propyl hydroxy n-propoxy acetate, isopropyl hydroxyisopropoxy acetate, n-butyl hydroxy n-butoxy acetate, and the like.
本発明で用いられる２−（Ｎ置換アミノメチル）
ピロリジンは、例えばプロリンから容易に製造す
ることができる〔Bull.Chem.Soc.Jpn.、51、1869
（1978）〕。具体的には２−（アニリノメチル）ピロ
リジン、２−（２，６−キシリジノメチル）ピロ
リジン、２−（Ｎ−ｐ−トリルアミノメチル）ピ
ロリジン、２−（Ｎ−ナフチルアミノメチル）ピ
ロリジン等が好ましく用いられる。 2-(N-substituted aminomethyl) used in the present invention
Pyrrolidine can be easily produced from, for example, proline [Bull.Chem.Soc.Jpn., 51 , 1869
(1978)]. Specifically, 2-(anilinomethyl)pyrrolidine, 2-(2,6-xylidinomethyl)pyrrolidine, 2-(N-p-tolylaminomethyl)pyrrolidine, 2-(N-naphthylaminomethyl)pyrrolidine, etc. are preferred. used.
光学活性もしくはラセミの２−（Ｎ置換アミノ
メチル）ピロリジンとグリオキシル酸エステルも
しくはグリオキシル酸エステルヘミアセタールを
反応させることにより本発明のグリオキシル酸誘
導体を製造することができる。本反応に用いる溶
媒はベンゼン、トルエン、エーテル、クロロホル
ム、ヘキサン、ヘプタン等通常用いる有機溶媒で
よい。反応温度は特に限定されないが、通常汎用
される溶媒の沸点以下で行なうことができる。沸
点以上で反応させる場合は加圧系となるので密閉
容器中で実施する必要がある。反応の進行ととも
に生成する水はモレキユラーシーブ等の脱水剤ま
たは共沸によつて除去すればよい。ベンゼンまた
はトルエンを用いて共沸脱水する方法が容易かつ
経済的である。 The glyoxylic acid derivative of the present invention can be produced by reacting optically active or racemic 2-(N-substituted aminomethyl)pyrrolidine with glyoxylic acid ester or glyoxylic acid ester hemiacetal. The solvent used in this reaction may be a commonly used organic solvent such as benzene, toluene, ether, chloroform, hexane, heptane, etc. Although the reaction temperature is not particularly limited, it can be carried out at a temperature below the boiling point of a commonly used solvent. When the reaction is carried out at a temperature above the boiling point, a pressurized system is used, so it is necessary to carry out the reaction in a closed container. Water generated as the reaction progresses may be removed by a dehydrating agent such as a molecular sieve or by azeotroping. Azeotropic dehydration using benzene or toluene is easy and economical.
かくして得られたグリオキシル酸誘導体はカラ
ムクロマトグラフイーあるいは蒸留により精製で
きるが、反応溶媒を留去したのみの粗生成物でも
高純度のものとして得ることができる。以下の実
施例で本発明の具体的な説明をする。 The glyoxylic acid derivative thus obtained can be purified by column chromatography or distillation, but even a crude product obtained by simply distilling off the reaction solvent can be obtained in high purity. The present invention will be specifically explained in the following examples.
実施例 １
ヒドロキシメトキシ酢酸メチル638mgと（Ｓ）−
２−（アニリノメチル）ピロリジン1.00ｇをベン
ゼン10mlに溶解し、共沸で水を除去しながら30分
間還流した。溶媒を減圧下に留去し1.38ｇのグリ
オキシル酸誘導体である２−カルボメトキシ−３
−フエニル−１，３−ジアザビシクロ〔3.3.0〕
オクタンを得た。Example 1 638 mg of methyl hydroxymethoxyacetate and (S)-
1.00 g of 2-(anilinomethyl)pyrrolidine was dissolved in 10 ml of benzene and refluxed for 30 minutes while removing water azeotropically. The solvent was distilled off under reduced pressure to obtain 1.38 g of 2-carbomethoxy-3, a glyoxylic acid derivative.
-Phenyl-1,3-diazabicyclo[3.3.0]
Got octane.
nmrピークはδ（ppm）＝1.5〜2.3（4H、マルチ
プレツト）、2.3〜4.1（5H、マルチプレツト）、3.5
（3H、シングレツト）、4.6（1H、シングレツト）、
6.2〜7.1（5H、マルチプレツト）であつた。 nmr peaks are δ (ppm) = 1.5-2.3 (4H, multiplet), 2.3-4.1 (5H, multiplet), 3.5
(3H, singlet), 4.6 (1H, singlet),
It was 6.2-7.1 (5H, multiplet).
アルミナカラムおよびシヨートパス蒸留により
精製したものの元素分析値は次の通りであつた。 The elemental analysis values of the product purified by an alumina column and short pass distillation were as follows.
元素分析
Ｃ Ｈ Ｎ
実測値 68.26％ 7.64％ 11.65％
計算値 68.27％ 7.37％ 11.37％
実施例 ２
ヒドロキシメトキシ酢酸メチルの代わりにグリ
オキシル酸メチル500mgを用いた他は実施例１と
同様に反応を行ない1.38ｇの２−カルボメトキシ
−３−フエニル−１，３−ジアザビシクロ
〔3.3.0〕オクタンを得た。Elemental analysis C H N Actual value 68.26% 7.64% 11.65% Calculated value 68.27% 7.37% 11.37% Example 2 The reaction was carried out in the same manner as in Example 1 except that 500 mg of methyl glyoxylate was used instead of methyl hydroxymethoxyacetate. g of 2-carbomethoxy-3-phenyl-1,3-diazabicyclo[3.3.0]octane was obtained.
実施例 ３
ヒドロキシメトキシ酢酸メチルの代わりにヒド
ロキシエトキシ酢酸エチル842mgを用いた他は実
施例１と同様に反応を行ない1.44ｇの２−カルボ
エトキシ−３−フエニル−１，３−ジアザビシク
ロ〔3.3.0〕オクタンを得た。Example 3 The reaction was carried out in the same manner as in Example 1, except that 842 mg of ethyl hydroxyethoxy acetate was used instead of methyl hydroxymethoxy acetate, and 1.44 g of 2-carboethoxy-3-phenyl-1,3-diazabicyclo [3.3.0 ] Obtained octane.
nmrピークはδ（ppm）＝1.2（3H、トリプレツ
ト）、1.5〜2.3（4H、マルチプレツト）、2.3〜4.1
（5H、マルチプレツト）、4.0（2H、カルテツト）、
4.6（1H、シングレツト）、6.2〜7.1（5H、マルチ
プレツト）であつた。 nmr peaks are δ (ppm) = 1.2 (3H, triplet), 1.5-2.3 (4H, multiplet), 2.3-4.1
(5H, multiplet), 4.0 (2H, quartet),
4.6 (1H, singlet) and 6.2-7.1 (5H, multiplet).
実施例 ４
ヒドロキシメトキシ酢酸メチルの代わりにグリ
オキシル酸−ｎ−ブチル740mgを用いた他は実施
例１と同様に反応を行ない、1.60ｇの２−カルボ
ブトキシ−３−フエニル−１，３−ジアザビシク
ロ〔3.3.0〕オクタンを得た。Example 4 The reaction was carried out in the same manner as in Example 1, except that 740 mg of n-butyl glyoxylate was used instead of methyl hydroxymethoxyacetate, and 1.60 g of 2-carbobutoxy-3-phenyl-1,3-diazabicyclo[ 3.3.0] Obtained Octane.
nmrピークはδ（ppm）＝0.7〜2.3（11H、マルチ
プレツト）、2.3〜4.1（5H、マルチプレツト）、3.9
（2H、トリプレツト）、4.6（1H、シングレツト）、
6.2〜7.1（5H、マルチプレツト）であつた。 The nmr peaks are δ (ppm) = 0.7 to 2.3 (11H, multiplet), 2.3 to 4.1 (5H, multiplet), 3.9
(2H, triplet), 4.6 (1H, singlet),
It was 6.2-7.1 (5H, multiplet).
参考例 １
ヒドロキシメトキシ酢酸1.89ｇと（Ｓ）−２−
（アニリノメチル）ピロリジン2.64ｇを用いて実
施例１と同様に反応を行ない、得られた２−カル
ボメトキシ−３−フエニル−１，３−ジサザビシ
クロ〔3.3.0〕オクタンを75mlのテトラヒドロフ
ランに溶解した。無水塩化マグネシウム1.57ｇを
加え10分間加熱還流した後、−70℃に冷却した。
メチルマグネシウムブロミドのエーテル溶液1.36
倍当量を滴下し、１時間反応させた後、飽和塩化
アンモニウム水溶液10mlを加え、室温まで昇温さ
せた。反応液をエーテルで抽出し飽和食塩水で洗
浄後芒硝で乾燥させた。減圧下溶媒を留去し得ら
れた残留物をアルミナカラムで精製して2.499ｇ
（72％）の２−アセチル−３−フエニル−１，３
−ジアザビシクロ〔3.3.0〕オクタンを得た。Reference example 1 1.89g of hydroxymethoxyacetic acid and (S)-2-
A reaction was carried out in the same manner as in Example 1 using 2.64 g of (anilinomethyl)pyrrolidine, and the obtained 2-carbomethoxy-3-phenyl-1,3-disazabicyclo[3.3.0]octane was dissolved in 75 ml of tetrahydrofuran. After adding 1.57 g of anhydrous magnesium chloride and heating under reflux for 10 minutes, the mixture was cooled to -70°C.
Ether solution of methylmagnesium bromide 1.36
Double equivalent amount was added dropwise, and the mixture was reacted for 1 hour. Then, 10 ml of saturated ammonium chloride aqueous solution was added, and the temperature was raised to room temperature. The reaction solution was extracted with ether, washed with saturated brine, and dried over sodium sulfate. The solvent was distilled off under reduced pressure and the resulting residue was purified using an alumina column to give 2.499g.
(72%) of 2-acetyl-3-phenyl-1,3
-Diazabicyclo[3.3.0]octane was obtained.
nmrピークはδ（ppm）＝1.5〜2.2（4H、マルチ
プレツト）、1.9（3H、シングレツト）、2.4〜3.3
（3H、マルチプレツト）、3.5〜3.9（2H、マルチプ
レツト）、4.1（1H、シングレツト）、6.1〜7.1
（5H、マルチプレツト）であつた。 nmr peaks are δ (ppm) = 1.5-2.2 (4H, multiplet), 1.9 (3H, singlet), 2.4-3.3
(3H, multiplet), 3.5 to 3.9 (2H, multiplet), 4.1 (1H, singlet), 6.1 to 7.1
(5H, multiplet).
参考例 ２
参考例１で得られた２−アセチル−３−フエニ
ル−１，３−ジアザビシクロ〔3.3.0〕オクタン
258mgをエーテル５mlに溶解し−70℃に冷却し、
フエニルマグネシウムブロミドのエーテル溶液２
倍当量を加え１時間反応させた。飽和塩化アンモ
ニウム水溶液３mlを加え室温まで昇温させた。エ
ーテル層を分離し、１規定水酸化ナトリウム水溶
液で洗浄後２％塩酸11mlを加え０℃で12時間反応
させた。Reference Example 2 2-acetyl-3-phenyl-1,3-diazabicyclo[3.3.0]octane obtained in Reference Example 1
Dissolve 258 mg in 5 ml of ether and cool to -70°C.
Ether solution of phenylmagnesium bromide 2
Two equivalents were added and reacted for 1 hour. 3 ml of saturated ammonium chloride aqueous solution was added, and the temperature was raised to room temperature. The ether layer was separated, washed with 1N aqueous sodium hydroxide solution, 11 ml of 2% hydrochloric acid was added, and the mixture was reacted at 0°C for 12 hours.
エーテル層を分離し飽和食塩水で洗浄後、芒硝
で乾燥した。減圧下エーテルを留去し、得られた
残留物をシリカゲルカラム精製し128mg（76％）
の（Ｒ）−２−ヒドロキシ−２−フエニルプロピ
オンアルデヒドを得た。 The ether layer was separated, washed with saturated brine, and dried over Glauber's salt. Ether was distilled off under reduced pressure, and the resulting residue was purified with a silica gel column to yield 128 mg (76%).
(R)-2-hydroxy-2-phenylpropionaldehyde was obtained.
〔α〕D＝−255゜（Ｃ＝1.060、ベンゼン）で光学
収率は99％であつた。 [α] D = -255° (C = 1.060, benzene) and the optical yield was 99%.
Claims (1)
す） で示される光学活性もしくはラセミのグリオキシ
ル酸誘導体。 ２ グリオキシル酸エステルもしくはグリオキシ
ル酸エステルヘミアセタールと一般式(2) （式中、Ａはアリール基を表わす） で示される光学活性もしくはラセミの２−（Ｎ置
換アミノメチル）ピロリジンを反応させることを
特徴とする一般式(1) （式中、Ａはアリール基、Ｒはアルキル基を表わ
す） で示される光学活性もしくはラセミのグリオキシ
ル酸誘導体の製造法。[Claims] 1 General formula (1) (In the formula, A represents an aryl group and R represents an alkyl group.) An optically active or racemic glyoxylic acid derivative represented by the following formula. 2 Glyoxylic acid ester or glyoxylic acid ester hemiacetal and general formula (2) (In the formula, A represents an aryl group) General formula (1) characterized by reacting an optically active or racemic 2-(N-substituted aminomethyl)pyrrolidine (In the formula, A represents an aryl group and R represents an alkyl group.) A method for producing an optically active or racemic glyoxylic acid derivative represented by the following formula.
Priority Applications (10)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP7036579A JPS55162786A (en) | 1979-06-04 | 1979-06-04 | Glyoxylic acid derivative and its preparation |
| US06/089,356 US4337346A (en) | 1978-11-02 | 1979-10-30 | α-Hydroxyaldehyde and a process for preparing the same |
| EP81108506A EP0050351B1 (en) | 1978-11-02 | 1979-11-02 | Optically active or racemic alpha-hydroxyaldehydes and benzyl derivatives thereof |
| EP79302419A EP0011417B1 (en) | 1978-11-02 | 1979-11-02 | Optically active or racemic aminal derivatives, process for preparing same and for converting same to alpha-hydroxyaldehydes |
| EP81108507A EP0048501B1 (en) | 1978-11-02 | 1979-11-02 | Optically active or racemic diazabicyclooctane derivatives |
| DE7979302419T DE2965322D1 (en) | 1978-11-02 | 1979-11-02 | Optically active or racemic aminal derivatives, process for preparing same and for converting same to alpha-hydroxyaldehydes |
| DE8181108506T DE2967419D1 (en) | 1978-11-02 | 1979-11-02 | Optically active or racemic alpha-hydroxyaldehydes and benzyl derivatives thereof |
| DE8181108507T DE2966001D1 (en) | 1978-11-02 | 1979-11-02 | Optically active or racemic diazabicyclooctane derivatives |
| US06/257,587 US4383122A (en) | 1978-11-02 | 1981-04-27 | Process for preparing α-hydroxyaldehyde |
| US06/457,666 US4584387A (en) | 1978-11-02 | 1983-01-13 | Acyl and ester derivatives of 1,3-diazabicyclo[3,3,0]octane |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP7036579A JPS55162786A (en) | 1979-06-04 | 1979-06-04 | Glyoxylic acid derivative and its preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS55162786A JPS55162786A (en) | 1980-12-18 |
| JPS6363546B2 true JPS6363546B2 (en) | 1988-12-07 |
Family
ID=13429328
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP7036579A Granted JPS55162786A (en) | 1978-11-02 | 1979-06-04 | Glyoxylic acid derivative and its preparation |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS55162786A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4643424B2 (en) * | 2005-12-02 | 2011-03-02 | 三栄源エフ・エフ・アイ株式会社 | Method for producing 2-acetyl-1-pyrroline |
-
1979
- 1979-06-04 JP JP7036579A patent/JPS55162786A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS55162786A (en) | 1980-12-18 |
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